Nausea and vomiting in pregnancy (NVP) in Chinese pregnant women: a cross-sectional study

Background This study addresses the scarcity of research on nausea and vomiting in pregnancy (NVP) in China. It aims to explore the current NVP status in the country using validated questionnaires, analyze associated factors, and provide a useful reference for future research. The study also compares results from different assessment tools. Methods Online questionnaires were utilized to gather data from 535 pregnant women across 24 provinces. Demographic, pregnancy, and NVP-related information were collected. NVP severity was assessed using Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) and the Rhodes Index of Nausea, Vomiting, and Retching (RINVR) scales. Ordinal logistic regression identified factors linked to NVP severity. Differences between PUQE and RINVR assessments were compared. Results NVP prevalence exceeded 90%, with 96.1% assessed by PUQE and 90.8% by RINVR. Incidence decreased from nausea to retching and vomiting. Severe NVP correlated with reduced gestational weight gain, younger age, fewer gestational weeks, and living in North (all P values < 0.05). There was moderate consistency between PUQE and RINVR assessments. The NVP prevalence assessed by the PUQE is higher than that assessed by the RINVR in the same population. However, the proportion of NVP levels above moderate assessed by RINVR is greater than that assessed by PUQE. Conclusions NVP is highly prevalent among Chinese pregnant women, with nausea being predominant. RINVR assessments may be better able to identify severe NVP, thereby improving the low treatment rates for severe NVP. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-024-06686-7.


Introduction
Nausea and vomiting in pregnancy (NVP) is a common complication during pregnancy, typically occurring in early pregnancy and subsiding during mid-pregnancy.However, for a minority of women, it persists into late pregnancy.Previous studies have indicated that 60-90% of pregnant women experience nausea and vomiting in pregnancy [1,2].NVP generally encompasses three symptoms: nausea, vomiting, and retching [3].Although rare, there have been reports of maternal deaths or fetal demise caused by severe NVP.Severe cases, known as hyperemesis gravidarum, can lead to psychological distress and fear in pregnant women, influencing their decisions about continuing the pregnancy [4].Additionally, severe NVP has been associated with severe clinical outcomes such as esophageal rupture, pneumothorax, Wernicke's encephalopathy, and splenic rupture [5].Recent studies have also identified several adverse fetal outcomes associated with severe NVP, including psychiatric disorders [6], cardiovascular diseases [7], and respiratory morbidity [8].
The previous studies on this topic had one or more of the following limitations: 1.The research was conducted on samples from a single city, which may not adequately represent the overall prevalence of NVP in China.2. While some studies had a large sample size, they did not employ standardized questionnaires with good reliability and validity to assess NVP. 3.Even when reliable questionnaires like PUQE were used, the descriptions of the three distinct symptoms of NVP, including nausea, vomiting, and retching, were insufficient.
These limitations in prior research highlight the need for a more comprehensive and representative study of NVP in China, considering the diverse population and geographical variations across the country.
Currently, the commonly used questionnaire to investigate the status of NVP is PUQE.This questionnaire, recommended by the American College of Obstetricians and Gynecologists in their guidelines, consists of three questions: duration of nausea, frequency of vomiting, and frequency of retching [18].However, PUQE assesses each of the three different symptoms using only one dimension, providing a less comprehensive description of NVP.
RINVR, developed by Rhodes, is a questionnaire that has been validated for assessing nausea and vomiting symptoms.It comprises eight questions, evaluating the duration and frequency of nausea and the level of distress caused; the frequency of vomiting, the average volume per episode, and the distress level caused; and the frequency of retching and the level of distress caused [3].Compared to PUQE, RINVR provides a more comprehensive and detailed assessment of NVP symptoms.While RINVR is commonly used to assess postoperative or chemotherapy-induced nausea and vomiting, there has been limited research utilizing RINVR to evaluate NVP.Furthermore, there are currently no studies in China that have utilized RINVR to investigate NVP.This presents an opportunity for future research to employ RINVR for a more thorough understanding of NVP symptoms in the Chinese population.
Based on the information provided, we conducted an online questionnaire survey and utilize both PUQE and RINVR to investigate the current status of NVP across 24 of the 34 provincial-level administrative divisions in China.The objectives of this research are as follows: (1) Survey the current status of NVP in China using validated questionnaires.( 2) Analyze demographic characteristics related to NVP. (3) Compare the assessment of NVP using PUQE and RINVR.

Study design and setting
This study adopts a cross-sectional research design, conducting an online questionnaire survey to investigate the prevalence of NVP among pregnant women in China.

Participants
This study is a sub-study of "The Effect of 5 Foods Containing Antiemetic Food Extract on the Improvement of Nausea and Vomiting of Pregnancy: A Randomized Study." This RCT recruited participants across China using an online screening questionnaire.Participants were invited to fill out the screening questionnaire by scanning a QR code provided on an online platform.Researchers then contacted participants via the phone numbers provided in the questionnaire to verify the information (e.g., addressing incomplete responses or logical inconsistencies).Participants for this sub-study were recruited from pregnant women who completed the online screening questionnaire for the main study and whose questionnaires passed the completeness and logical consistency checks.

Sample size
For this cross-sectional survey employing multifactor regression analysis, a sample size of 5 to 10 times the total number of study variables was targeted [19].With 12 variables in consideration, the required sample size ranged from 60 to 120 participants.Allowing for a 10% non-response rate, 66 to 132 participants were deemed necessary.

Variables
This study collected the following participant information: (1) General Information: Including age, height, prepregnancy weight, current weight, educational level and Internet Protocol (IP) address, which was used to distinguish the residence of participants.Based on the IP address, if it is located north of the Qinling-Huaihe Line, which is the geographical dividing line between northern and southern China, the residence is classified as North.If it is located south of the Qinling-Huaihe Line, the residence is classified as South.(2) Pregnancy Details: Current gestational age, number of pregnancies, number of deliveries, and fetal count.(3) Medical History: Whether participants were currently taking medications for treating NVP.(4) Assessment of NVP: Scores obtained from PUQE and RINVR evaluations.

Data source
All variables were collected through self-administered online questionnaires completed by pregnant women.An online questionnaire was created on the Questionnaire Star platform which was opened from February 22, 2023 to February 10, 2024, and participants were recruited through various social platforms such as WeChat groups for expectant mothers and the Kangaroo Mother WeChat official account.
Participants could access and complete the questionnaire by scanning a QR code.At the end of the questionnaire, participants were required to provide their phone numbers for contact purposes in case verification of questionnaire responses was necessary.
The questionnaire's introduction provided detailed guidance for participants as follows: "Dear expectant mothers, please fill out the following questionnaire to preliminarily assess if you meet the inclusion criteria for our study.Please select the options that best reflect your experience of NVP.Definitions of symptoms are as follows: Vomiting: The act of expelling stomach or intestinal contents due to discomfort.
Retching: The motion of vomiting without expelling stomach or intestinal contents.
Nausea: The feeling of sick in the upper abdomen without actual vomiting or retching.
Two researchers independently screened and checked the questionnaires.If logical errors were detected, such as an unrealistically high current weight (e.g., 150 kg), the researchers contacted the questionnaire respondents by phone to verify and correct the information.Finally, questionnaires independently checked by two researchers were cross verified.In cases of inconsistencies, respondents were contacted again for clarification.

NVP assessment
This study employed the PUQE and RINVR questionnaires to assess NVP in pregnant women.

RINVR questionnaire
RINVR, developed by Rhodes and validated for reliability and validity, assesses immediate experiences of nausea and vomiting, such as those occurring within the past 24 h.RINVR comprises eight questions across three dimensions: nausea, vomiting, and retching/dry heaves.The questions include details such as the number of episodes of vomiting and retching, the level of distress experienced, and the duration of symptoms.Each question has five response options, scored from 0 to 4. The total RINVR score ranges from 0 to 32.A score of 0 indicates no NVP, scores from 1 to 8 represent mild NVP, scores from 9 to 16 indicate moderate NVP, scores from 17 to 24 represent severe NVP, and scores from 25 to 32 indicate extremely severe symptoms.

Statistical analysis
All statistical analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).Normality tests revealed non-normal distribution of all quantitative variables.Hence, median and interquartile range (IQR) were used for describing quantitative variables.Categorical variables were described using frequencies and percentages.
Comparisons between groups for quantitative variables were conducted using the Mann-Whitney U test, while chi-square tests were employed for categorical variables.
The relationship between demographic/periodic features and NVP was analyzed through ordinal logistic regression.PUQE-assessed NVP severity and RINVR-assessed NVP severity were used as dependent variables, and demographic/periodic features were used as independent variables.Initial univariate analyses were performed, and variables showing statistical significance were included in the multivariate analysis.
As PUQE categorized NVP into 4 levels and RINVR into 5 levels, RINVR categories were consolidated into 4 levels (no NVP, mild NVP, moderate NVP, and severe NVP, with 'severe' combining the original 'great' and 'severe' categories) for comparison with PUQE.Discrepancies between PUQE and RINVR assessments were analyzed using the CMH chi-square test and Kappa consistency test.A significance level of P < 0.05 was considered statistically significant.

Participants
A total of 562 pregnant women completed the survey questionnaires.Among them, 27 questionnaires had issues and could not be verified due to incorrect or missing phone numbers.Consequently, 535 questionnaires were included in the final analysis.

Univariate analysis of factors influencing NVP NVP degree assessed by PUQE as dependent variables
As indicated in Table 3, pregnant women with GW less than 14 weeks (P = 0.0001) and those who took treatment measures (P = 0.001) experienced higher severity of NVP.
Pregnant women with more severe NVP had lesser GWG (P < 0.0001).There were no statistically significant differences in the severity of NVP based on age, pre-pregnancy BMI, gestational times, parity times, education level, number of fetuses, or residence.

NVP degree assessed by RINVR as dependent variables
As shown in Table 4, pregnant women under the age of 35 (P = 0.001), those with GW less than 14 weeks (P < 0.0001), residing in the northern regions (P = 0.003), and those taking treatment measures (P = 0.009) experienced higher severity of NVP.Pregnant women with more severe NVP had lesser GWG (P < 0.0001).No significant correlations were found between NVP severity and other factors.

Multivariate analysis of factors related to NVP PUQE assessment results as dependent variables
As shown in Table 5, after controlling for GW and treatment measures, pregnant women with severe NVP had lesser GWG compared to those without NVP (P = 0.002).a NVP, nausea and vomiting during pregnancy.b PUQE, Pregnancy-Unique Quantification of Emesis and Nausea.c GW, gestational week; d GWG, gestational week gain.

RINVR assessment results as dependent variables
As depicted in Table 6, older age and later gestational age, as well as residing in southern China, were independently associated with lower severity of NVP.Pregnant women with severe and great NVP experienced lesser weight gain during pregnancy.

Prevalence of NVP in Chinese pregnant women
This study demonstrates that regardless of whether the PUQE or RINVR assessment methods were employed, the prevalence rate of NVP in Chinese pregnant women exceeded 90%.This is close to the 90.9% [20] reported by Oi Ka Chan and colleagues, slightly higher than the 84.1-87.5% reported in other Chinese studies [9,17].Several factors might contribute to this variance.First, the diverse assessment methods used in different studies could lead to varied prevalence rates.This study utilized validated and standardized PUQE and RINVR questionnaires.Second, the sample in this study represented 24 provinces in China, enhancing its representativeness compared to previous studies.The prevalence of NVP among Chinese pregnant women, as indicated by this study, is also higher than that reported in Spain (63.5%) [21], Canada (63.3%) [22], and the United States (68.6%) [23].Additionally, the high prevalence of NVP in China may be related to the low smoking rates among Chinese women.Research indicates that pre-pregnancy smoking can reduce the  risk of NVP by increasing growth differentiation factor 15 (GDF15) levels, whereas non-smokers typically have lower GDF15 levels [24][25][26].GDF15 is correlated with NVP, interacting with the Glial-derived neurotrophic factor receptor alpha-like (GFRAL) protein, a key pathogenic mechanism of NVP [27].Pre-pregnancy exposure to higher levels of GDF15 can desensitize women to the rapid increase in GDF15 during early pregnancy, thereby alleviating NVP symptoms [28].According to a study, the smoking rate among Chinese women remained between 2.2% and 1.9% from 2007 to 2018 [29].Another study reported that the smoking rate among Chinese women was about 3.4% in 2010, indicating a generally low smoking trend [30].Therefore, the low smoking rate among Chinese women may help explain the higher prevalence of NVP in China.

Different NVP symptoms among Chinese pregnant women
When considering different NVP symptoms, the frequency of nausea, retching, and vomiting among Chinese pregnant women decreases in that order.According to the RINVR assessment results, the distress caused by nausea and retching is stronger than that caused by vomiting, possibly due to the higher frequency of nausea and  retching.Vomiting represents the final symptom in the progression of NVP, involving a complex reflex action that can be divided into three stages: nausea, retching, and vomiting [3].During nausea, gastric tension and peristalsis weaken, while duodenal tension increases, possibly accompanied by duodenal reflux.Retching involves relaxation of the upper part of the stomach and brief contraction of the gastric antrum.Vomiting occurs when the gastric antrum continues to contract, the lower esophageal sphincter relaxes, abdominal muscles contract, the diaphragm descends, abdominal pressure increases, forcing gastric contents to rapidly and violently reflux from the stomach, through the esophagus and mouth, and out of the body [31].Recent research has found that GDF15 derived from the fetoplacental unit is highly likely to be the cause of NVP.Studies have shown that in early pregnancy, the levels of GDF15 in maternal blood appear alongside NVP symptoms and show a strong correlation with these symptoms.Whole exome sequencing has identified GDF15 as the strongest risk factor associated with severe NVP [32].Furthermore, GDF15 has also been shown to be related to symptoms such as loss of appetite, taste aversion, nausea, vomiting, and weight loss [33][34][35][36][37][38].The latest research continues to support that GDF15 derived from the fetoplacental unit is highly likely to be a causal factor of NVP [28].HCG was previously thought to be associated with the occurrence and severity of NVP, but genetic studies did not find any association with the hCG gene or receptor [32].

Factors related to NVP
Multivariate analysis revealed a consistent finding with other studies: more severe NVP correlates with lesser weight gain during pregnancy, a phenomenon noted in previous research as well [21,39,40].Symptoms like nausea, vomiting, and retching may diminish a pregnant woman's appetite, leading to reduced food intake and digestion, consequently resulting in lower weight gain during pregnancy [41].This study also found that older age and later gestational weeks are associated with lower severity of NVP, aligning with similar findings in other research studies [20,42].Previous studies have found a correlation between multiple pregnancies and the severity of NVP [42].However, our study did not find a statistically significant association between multiple pregnancies and NVP.This may be due to the small sample size, as our study included only 11 cases of multiple pregnancies, and the NVP severity in these 11 cases was all rated as 'Moderate' by PUQE.To explore the relationship between multiple pregnancies and NVP further, future research should include a larger sample size of multiple pregnancies.
This study is the first to compare the severity of NVP between Northern and Southern China.In a multifactorial analysis using the RINVR to assess NVP severity, we found that the rate of severe NVP was lower in Southern China compared to Northern China.Since no previous studies directly analyzed the differences in NVP severity between the North and South, we reviewed literature investigating the prevalence of NVP in China.We identified three studies [10,13,43] with settings that could be categorized as either Northern or Southern China.Two studies [13,43] conducted in Southern China had a combined sample size of 4,654 participants, with 2,277 (48.9%) experiencing mild NVP, 1,229 (26.4%) experiencing moderate NVP, and 61 (1.3%) experiencing severe NVP.One study used the PUQE questionnaire [13], while the other used a self-developed questionnaire [43].One study conducted in Northern China [10] had a sample size of 3,064 participants, with 299 (9.8%) experiencing severe NVP, assessed by asking participants, "Have you experienced severe nausea and vomiting during early pregnancy accompanied by urinary ketone positivity?(Yes/No)." Severe NVP was defined as persistent or aggravated nausea and vomiting in early pregnancy, accompanied by ketonuria.These studies indicate a higher incidence of severe NVP in Northern China, consistent with our findings that Northern patients have a higher prevalence of severe NVP.
We further classified patients into six regions based on the Chinese six-region division method and their IP addresses: Central-South China, East China, North China, Northeast China, Northwest China, and Southwest China.We then grouped the patients and calculated the percentage of "Severe" and "Great" NVP levels assessed by the RINVR questionnaire in each region.The percentages from highest to lowest were East China (27 [54%]), North China (52.7%),Northwest China (5 [45.5%]),Central-South China (20 [35.5%]),Southwest China (137 [34.9%]), and Northeast China (1 [25%]).This analysis revealed that the combined percentages of "Severe" and "Great" levels exceeded 40% in East China, North China, and Northwest China, while they were below 40% in Central-South China, Southwest China, and Northeast China.Due to the sample size limitations, further analysis at the provincial or municipal level was not feasible.
China's vast territory encompasses diverse geographic and climatic characteristics, dietary habits, and perceptions of NVP.The differences in NVP severity between Northern and Southern China may be related to these geographic, climatic, and cultural factors, as well as differing attitudes toward NVP symptoms.Our study suggests that Northern pregnant women and obstetric healthcare providers should pay closer attention to NVP due to its association with adverse maternal and fetal outcomes.
In summary, this is an interesting finding that warrants further research specifically on the differences in NVP between Northern and Southern China.Future studies should collect detailed information on NVP, diet, physical activity, and perceptions of NVP among patients and their families to explore potential factors contributing to the differences in NVP severity between the regions.

Comparison of NVP assessment between PUQE and RINVR
Both PUQE and RINVR were proved validated for assessing NVP in previous studies [44,45].This study found a moderate consistency between the NVP severity assessed by PUQE and RINVR, indicating some differences.
Firstly, the NVP prevalence assessed by the PUQE is higher than that assessed by the RINVR in the same population.This discrepancy may arise because the two questionnaires evaluate different time spans.PUQE assesses the NVP condition over the entire pregnancy up to the point of filling out the questionnaire [46,47], while RINVR assesses the patient's condition over the past 24 h at the time of questionnaire completion [48].The frequency and severity of NVP symptoms may fluctuate throughout pregnancy, especially after the first trimester (27.3% of the patients in this study were beyond 14 weeks of gestation) [49].It is possible that the symptoms had eased or were absent the day before the patient filled out the RINVR, leading to a lower prevalence and severity level compared to PUQE, even though RINVR includes more items.
Secondly, after combining the "Great" and "Severe" levels assessed by RINVR, the combined "Severe" rate is actually higher than the "Severe" rate assessed by PUQE.This might be due to the same reason as the first issue, i.e., the different time spans assessed by PUQE and RINVR.Additionally, the difference in NVP severity classification between PUQE and RINVR might contribute to this discrepancy.PUQE classifies NVP into four levels: None, Mild, Moderate, and Severe.In contrast, RINVR divides NVP into five levels: None, Mild, Moderate, Great, and Severe.In this study, among the patients classified as "Great" by RINVR (145 patients), 20 were classified as "Severe" (PUQE score ≥ 13), 124 as "Moderate" (PUQE score 7-12), and 1 as "Mild" (PUQE score 4-6) according to PUQE.These data suggest that most patients rated as "Great" by RINVR might fall into the "Moderate" category according to PUQE, with a smaller portion falling into the "Severe" category.This indicates that using PUQE may lead to some underdiagnosis and undertreatment.As previously mentioned, severe NVP is associated with adverse pregnancy and fetal outcomes.Therefore, RINVR may be a more suitable tool for improving these outcomes.Additionally, RINVR assesses a broader range of symptoms, including the distress caused by nausea, retching, and vomiting, providing a more comprehensive understanding of NVP experiences.

Strengths and limitations
This study has several limitations.First, this study was conducted through an online self-administered questionnaire, which may result in selection bias, because pregnant women who have NVP-related symptoms are more willing to fill in the questionnaire.This may also be one of the reasons why this study found that the prevalence of NVP in China is higher.Second, this study did not conduct stratified sampling according to different regions in China, which may limit the representativeness of the sample in this study.However, this study is the first nationwide NVP survey in China, involving 24 provinces/autonomous regions/municipalities, and the sample is still representative of China.In addition, this study found differences in the prevalence and severity of NVP between northern and southern China, which guides subsequent studies to further study the differences in NVP in different regions of China, and has guiding significance for formulating corresponding NVP intervention strategies for different regions in China.Finally, this study was the first to compare the differences between PUQE and RINVR in assessing NVP levels in China and found that PUQE may underestimate the degree of NVP in patients.Considering that severe NVP is associated with adverse outcomes for both mothers and fetuses, we suggest that regular assessment using RINVR may be better.Additionally, one limitation of our study is that the PUQE and RINVR tools assess symptoms over different time spans, which might contribute to the differences observed in the results.Further studies are needed to compare the two tools covering the same time span in China.

Conclusions
This cross-sectional study revealed a high prevalence of NVP among Chinese pregnant women, with age, gestational age, living in South and gestational weight gain showing a negative correlation with the severity of NVP.These findings enhance our understanding of NVP in the Chinese population and provide a useful reference for future research.Both PUQE and RINVR prove useful for NVP assessment.However, RINVR assessments may be better able to identify severe NVP, thereby improving the low treatment rates for severe NVP.

Table 1
General characteristic of participants a IQR, inter quartile range; b BMI, body mass index; c GWG, gestational weight gain; d GW, gestational week

Table 2
NVP a assessment using PUQE b and RINVR c a NVP, nausea and vomiting during pregnancy.b PUQE, Pregnancy-Unique Quantification of Emesis and Nausea.c RINVR, the Rhodes Index of Nausea, Vomiting and Retching.d IQR, inter quartile range

Table 3
NVP a degree assessed by PUQE b between different groups a NVP, nausea and vomiting during pregnancy.b PUQE, Pregnancy-Unique Quantification of Emesis and Nausea.c GW, gestational week; d BMI, body mass index; e GWG, gestational week gain.f IQR, inter quartile range

Table 4
NVP a degree assessed by RINVR b between different groups a NVP, nausea and vomiting during pregnancy.b RINVR, the Rhodes Index of Nausea, Vomiting and Retching; c GW, gestational week; d BMI, body mass index; e GWG, gestational week gain.f IQR, inter quartile range

Table 5
Multiple logistic regression for NVP a degree assessed by PUQE b

Table 6
Multiple logistic regression for NVP a degree assessed by RINVR b a NVP, nausea and vomiting during pregnancy.b RINVR, the Rhodes Index of Nausea, Vomiting and Retching; c GW, gestational week; d GWG, gestational week gain

Table 7
Comparison of NVP a degree assessed by PUQE b and RINVR c a NVP, nausea and vomiting during pregnancy.b PUQE, Pregnancy-Unique Quantification of Emesis and Nausea.c RINVR, the Rhodes Index of Nausea, Vomiting and Retching